The first cohort of three subjects will receive PR610 at Dose Level 1. Subsequent cohorts will receive PR610 at a dose levels determined as per dose escalation criteria. The MTD will be defined as the dose level at which one (1) or fewer subject in six exhibit DLT with the next highest dose level demonstrating two (2) or more of six (6) subjects with DLT (or for which more than ≥33% of subjects exhibit DLT if the cohort size exceeds 6 subjects).

Is considered PR610-related, as defined by "Definitely-related", "Probably-related" or "Possibly-related"

Is clinically significant, as determined by the Principal Investigator

In addition, DLT will meet at least one of the criteria listed below using grading criteria from the CTCAEv4.

Grade 4 hematologic toxicity

Any drug-related toxicity that prevents administration of 100% of all doses of PR610 planned for Cycle 1

Grade 3 or higher non-hematologic toxicity

Secondary Outcome Measures:

Evaluate the safety profile of PR610: Adverse Events [ Time Frame: 30 days following the last administration of study treatment ] [ Designated as safety issue: Yes ]

The number of adverse events experienced by participants will be measured.

Peak Plasma Concentration (Cmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion [ Time Frame: pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2 ] [ Designated as safety issue: No ]

Evaluate the activity of PR610 in a general phase I population and in a subset of subjects with NSCLC genetically resistant to reversible EGFR inhibitors [ Time Frame: 30 days following the last administration of study treatment ] [ Designated as safety issue: No ]

Efficacy will be determined for each subject that received at least one dose of PR610 and had at least one post-baseline disease assessment. The following four outcomes will be tabulated:

Tumor response Time to response Duration of response Progression-free survival

Time of Peak Plasma Concentration (tmax) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion [ Time Frame: pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2 ] [ Designated as safety issue: No ]

Half life (t1/2) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion [ Time Frame: pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2 ] [ Designated as safety issue: No ]

Area Under the Curve (AUC) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion [ Time Frame: pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2 ] [ Designated as safety issue: No ]

Clearance (CL) of PR610 and PR610E for Both a 1-hour and a 24-hour Weekly Infusion [ Time Frame: pre, 30 minutes into infusion, end of infusion, 1, 2, 4, 24, 48, and 72 hours post-infusion on Cycles 1 and 2 ] [ Designated as safety issue: No ]

In the absence of progressive disease or unacceptable toxicity, subjects may continue to receive PR610. Intra-subject dose escalation (to no higher than the highest safe level) is allowed in subjects who are not experiencing dose limiting toxicity. Disease assessment will be repeated at week 6 and then every 8 weeks thereafter.

Pharmacokinetic (PK) assessment (PR610 and PR610E) will be performed for all subjects.

After determination of the MTD and the determination of the phase II dose, additional subjects with NSCLC that is genetically resistant to reversible EGFR inhibitors will be accrued into an expansion cohort.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Signed informed consent

Age 18 years or more

Histologically-confirmed, progressive cancer with the following diagnosis:

Phase I: locally advanced or metastatic solid tumor that may respond to an EGFR inhibitor;

At least 4 weeks from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation. Ongoing hormonal therapy administered for control of prostate cancer which may be continued through the study. In addition, in the phase II portion of the study, prior reversible EGFR tyrosine kinase inhibitor therapy, such as erlotinib or gefitinib, may be continued up to 48 hours prior to start of PR610 to prevent significant disease flare.

Recovered from prior treatment related toxicity

except for grade 1 fatigue, grade 1 peripheral sensory neuropathy and grade 1 or 2 alopecia during the phase I portion of the study

except for grade 1 toxicity, and grade 2 peripheral neuropathy during the phase II portion of the study

At least four (4) weeks from prior major surgery

Women of child-bearing potential must be willing to use an acceptable contraceptive method and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial

Sexually active men must be willing to use an acceptable contraceptive method

Cardiac left ventricular function with resting ejection fraction of less than 50%

Symptomatic CNS lesions or known CNS lesions that require therapy

Prior history of an allergic reaction to a tyrosine kinase inhibitor

Additional Exclusion Criteria during Expansion Phase

Any other malignancy likely to effect the assessment of toxicity or efficacy of PR610

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631279